Vascular risk factors (including hypertension and high cholesterol) during mid-life have been reported by many studies to increase the risk for dementia in later life. This has significant implications for dementia prevention as many vascular factors are modifiable. Most studies, however, have not explored these associations in the oldest-old (people 90 years and older) and it is not clear if the same vascular risk factors when present in very late-life are associated with increased risk of dementia and its related pathologies. In a preliminary study of oldest-old participants, we found a history of high blood pressure and history of high cholesterol to be less common in people who developed dementia compared to people who did not. Because at younger ages high blood pressure and high cholesterol are associated with increased dementia risk dementia, the relationship between these vascular factors and dementia appear to change with age. Thus, recommendations for treatment of vascular disease may be different for the very elderly as for younger people. We propose to study the association between vascular risk factors (namely hypertension and hypercholesterolemia) and risk of dementia in the oldest-old. A second objective is to generate new measures of microvascular pathologies in existing brains and investigate whether any association between vascular risk factors and dementia are mediated by vascular pathologies. Hypertension will be assessed in several different ways; by history collected when participants were on average 70 years of age, by history when participants were 90 years and older, and by direct blood pressure measurements at age 90 and older. Hypercholesterolemia will be similarly defined by history and direct lipid measurements obtained at age 90 and older. Intake of blood pressure and lipid lowering medications will be accounted for in the analyses of the associations. As this proposal is in response to an secondary data analysis announcement, most of the data to be analyzed has already been collected as part of The 90+ Study, one of the largest population-based studies of aging and dementia in people aged 90 years and older who have been extensively evaluated during life and a subset of them have agreed to undergo brain autopsy upon death. Vascular disease and dementia are both very common conditions in the oldest-old. As the oldest-old is the fastest growing segment of the population in the United States, dementia will become a public health epidemic in the coming decades. It is crucial to elucidate the association between potentially modifiable factors and dementia in this age group. If the associations between vascular risk factors and dementia change with age, the risks and benefits of treating vascular risk factors may also change with age. As much of current health practice relies on managing vascular disease, finding that reduced blood pressure and reduced cholesterol in the very elderly are not beneficial for cognitive health and its associated pathologies, and may even be harmful, disease management practices would need to be re-evaluated for the very elderly. PUBLIC HEALTH RELEVANCE: Vascular disease and dementia are both very common conditions in the oldest-old. As the oldest-old is the fastest growing segment of the population in the United States and many other countries, dementia threatens to become a public health epidemic in the coming decades. It is thus crucial to elucidate the association between potentially modifiable factors and dementia in this age group. As much of current health practice relies on managing vascular disease, finding that reduced blood pressure and reduced cholesterol in the very elderly are not beneficial for cognitive health and its associated pathologies, and may even be harmful, disease management practices would need to be re-evaluated for the very elderly.